Placental growth factor (PlGF) induced signalling regulates barrier properties of the retinal pigment epithelium (RPE)
Bibliographic record
Abstract
Purpose : It has been suggested that PlGF, as a key member of the VEGF-family, is associated with pathological angiogenesis, vasopermeability and neuroglial dysfunction in the inner retina (see review in Prog Ret Eye Res DOI: 10.1016/j.preteyeres.2018.10.006). Recent studies have indicated that PlGF may also play a role in outer retinal disease. We hypothesise that activation of the PlGF receptor pathway plays a pathogenic role in RPE dysfunction. Methods : Localisation of PlGF and its cognate receptors VEGFR-1 and neuropilin-1 (NRP-1) was assessed in murine and human retinal tissues using immunohistochemistry. Signalling responses to human recombinant PlGF was investigated in ARPE-19 and human foetal RPE (hfRPE). Tight junction integrity and RPE barrier properties were evaluated in ARPE-19 and hfRPE using transepithelial electrical resistance (TEER) measured at baseline and 24 hours after PlGF exposure in both normoxic and hypoxic conditions. A parallel assessment was made of RPE viability following PlGF exposure. Results : PlGF, VEGFR-1 and NRP-1 were localised to vascular cells, Müller glia and RPE in the retina. In vitro, the RPE demonstrated activation of VEGFR-1 and ERK1/2 upon exposure to PlGF (50ng/mL). PlGF disrupted integrity of the RPE tight junctions which was observed through mis-localisation of ZO-1. In terms of TEER, 50ng/mL PlGF reduced ARPE-19 ohms.cm2 by 32% (±2.63%) and hfRPE ohms.cm2 by 63% (±8.3%) and this was significantly different between control and 50ng/mL groups (ARPE-19 p <0.005; hfRPE p<0.05). There was no significant change in cell numbers however PlGF was associated with reduced RPE viability. Hypoxia exacerbated these PlGF effects in RPE. Conclusions : The key elements of the PlGF signalling pathway are present in human RPE in vitro and in vivo. PlGF has been shown to be upregulated in many disease scenarios and exposure to this growth factor compromises the RPE barrier suggesting that manipulation of this pathway could offer therapeutic benefits. This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".